The goal of this application is to understand the roles in vertebrate development of the nodal and nodal-related genes, genes that encode secreted intercellular signaling proteins in the TGF-beta/BMP family. It is proposed to test the following hypotheses: (1) that Xnr1 and Xnr2 are essential for normal mesoderm induction and patterning in vivo; (2) that sinistral Xnr1 expression is a causative factor in the development of left-right morphological laterality in vertebrates, and (3) that the left-specific expression of Xnr1 is under transcriptional control via cis-acting Xnr1 gene sequences.